We are studying the control of gene expression in Drosophila as involved in the phenomena of genetic suppression and enhancement and in the developmental and externally induced activities of the heat shock gene family. Certain spontaneously occurring mutations which correspond to the insertion of a transposable genetic element can place the expression of the gene at which the insertion occurs under the positive or negative control of other genes, called suppressors and enhancers, or more generally, modifiers. Modifiable insertion mutations are known in Drosophila, maize, bacteria, yeast and mice. We are employing genetic analysis and biochemical studies of transcription to understand the mechanisms by which modifiable insertions disrupt gene expression and by which they place expression of a locus under the control of modifier genes. In other studies, we are seeking to identify and characterize the DNA sequences responsible for transcriptional and translational control of the Drosophila heat shock genes in normal development and in response to ecdysterone and heat shock. We are carrying out interspecies comparisons of heat shock gene nucleotide sequences to identify conserved features of possible regulatory significance. We are also conducting transformation, transfection and in vivo analysis of the function of specific sequence features in heat shock gene regulation. The studies are intended to provide important and detailed knowledge regarding mechanisms of eukaryotic gene control, including hormonal control. In addition, they should yield important information regarding cellular control of and interactions with transposable genetic elements, possibly including retroviruses like those involved in certain neoplastic diseases.